CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer

Maciej Kmieciak, Andrea Worschech, Hooman Nikizad, Madhu Gowda, Mehran Habibi, Amy Depcrynski, Ena Wang, Kamar Godder, Shawn E. Holt, Francesco M. Marincola, Masoud H. Manjili

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Studies conducted in animal model of infectious diseases or H-Y antigen model suggest a crucial role for CD4+ T cells in providing help for CD8+ T-cell memory responses. This concept suggests that inclusion of T helper epitopes in vaccine formulation will result in improved CD8+ T-cell responses. Although this concept has been applied to cancer vaccine design, the role of CD4+ T cells in the memory differentiation of CD8+ T cells and retention of their anti-tumor function have never been tested in breast cancer model. Using the FVB mouse model of neupositive breast carcinoma we report for the first time that helpless T cells showed cytostatic or tumor inhibitory effects during primary tumor challenge whereas, helped T cells showed cytotoxic effects and resulted in complete tumor rejection. Such differential effects, in vivo, were associated with higher frequency of CD8+PD-L1+ and CD8+PD-1+ T cells in animals harboring helpless T cells as well as higher titer of IL-2 in the sera of animals harboring helped T cells. However, depletion of CD4+ T cells did not alter the ability of neu-specific CD8+ T cells to differentiate into memory cells and to retain their effector function against the tumor during recall challenge. These results suggest the inhibitory role of CD4+ T cells on CD8+ T-cell exhaustion without substantial effects on the differentiation of memory T cells during priming phase of the immune responses against breast cancer.

Original languageEnglish
Pages (from-to)385-394
Number of pages10
JournalBreast Cancer Research and Treatment
Volume126
Issue number2
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

Fingerprint

Breast Neoplasms
T-Lymphocytes
Neoplasms
H-Y Antigen
Cancer Vaccines
Aptitude
Cytostatic Agents
Interleukin-2
Communicable Diseases
Epitopes
Vaccines
Animal Models

Keywords

  • Breast cancer
  • CD4+ helper T cells
  • Helpless CD8+ T cells
  • HER-2/neu
  • Memory T cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer. / Kmieciak, Maciej; Worschech, Andrea; Nikizad, Hooman; Gowda, Madhu; Habibi, Mehran; Depcrynski, Amy; Wang, Ena; Godder, Kamar; Holt, Shawn E.; Marincola, Francesco M.; Manjili, Masoud H.

In: Breast Cancer Research and Treatment, Vol. 126, No. 2, 04.2011, p. 385-394.

Research output: Contribution to journalArticle

Kmieciak, M, Worschech, A, Nikizad, H, Gowda, M, Habibi, M, Depcrynski, A, Wang, E, Godder, K, Holt, SE, Marincola, FM & Manjili, MH 2011, 'CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer', Breast Cancer Research and Treatment, vol. 126, no. 2, pp. 385-394. https://doi.org/10.1007/s10549-010-0942-8
Kmieciak, Maciej ; Worschech, Andrea ; Nikizad, Hooman ; Gowda, Madhu ; Habibi, Mehran ; Depcrynski, Amy ; Wang, Ena ; Godder, Kamar ; Holt, Shawn E. ; Marincola, Francesco M. ; Manjili, Masoud H. / CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer. In: Breast Cancer Research and Treatment. 2011 ; Vol. 126, No. 2. pp. 385-394.
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